title: DNMT1-interacting RNAs block gene-specific DNA methylation.
abstract: DNA methylation was first described almost a century ago; however, the rules governing its establishment and maintenance remain elusive. Here we present data demonstrating that active transcription regulates levels of genomic methylation. We identify a novel RNA arising from the CEBPA gene locus that is critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extend the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene-selective demethylation of therapeutic targets in human diseases.
authors.affiliation: 1] Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [3] Università Cattolica del Sacro Cuore, Institute of Hematology, L.go A. Gemelli 8, Rome 00168, Italy [4].
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Ruscio
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Ebralidze
authors.forename: Touati
authors.initials: T
authors.lastname: Benoukraf
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amabile
authors.forename: Loyal A
authors.initials: LA
authors.lastname: Goff
authors.forename: Jolyon
authors.initials: J
authors.lastname: Terragni
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Figueroa
authors.forename: Lorena Lobo
authors.initials: LL
authors.lastname: De Figueiredo Pontes
authors.forename: Meritxell
authors.initials: M
authors.lastname: Alberich-Jorda
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.forename: Mengchu
authors.initials: M
authors.lastname: Wu
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Alò
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
authors.forename: Konstantin K
authors.initials: KK
authors.lastname: Ebralidze
authors.forename: Sriharsa
authors.initials: S
authors.lastname: Pradhan
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D012333:RNA, Messenger; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human